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Socioeconomic impact of chronic delta hepatitis in Spain: Indirect costs of work absenteeism, presenteeism, and premature mortality

Introduction Patients with chronic delta hepatitis (CDH) exhibit higher levels of morbimortality than those with hepatitis B only, generating higher indirect costs for society. The aim of this study was to estimate the loss of productivity and costs resulting from work absenteeism and presenteeism as well as premature mortality among patients with CDH in Spain. Methods Patients with CDH in their working age (between 20–65 years) were estimated by an epidemiological flow model that incorporated the prevalence of infection with the hepatitis B and D viruses. To calculate the costs (year-2023) of absenteeism and presenteeism (over a time horizon of 1 year) as well as premature mortality (i.e., the period from death to expected retirement age), as measured in years of productive life lost (YPLL), the human capital method was used. Specific variables pertaining to the Spanish labour market (working population with hepatitis D virus (HDV), working days, average number of hours worked and gross annual salary) were considered for each sex and age group and distinguished based on infection status. All parameters were obtained from the literature and Spanish databases. Results A total of 1,313 CDH patients of working ages (59% men, 41% women) and 97 patients who performed unpaid housework were identified. A total of 300,113 working hours were lost per year (29,015 hours/absenteeism and 271,098 hours/presenteeism), which entailed total annual costs of €4.5M (€536,400/absenteeism and €3.9M/presenteeism) related to CDH. Among patients of working ages, CDH was estimated to cause 28 annual deaths at a cost of €8.2 M, resulting in 449 YPLL at an average cost of €18,297/YPLL. The indirect costs were estimated to be € 12.7M. Conclusions CDH entails significant economic burdens for society. Consideration of the indirect costs associated with CDH is crucial with respect to the design of public health policies and interventions.

Multiplex detection of seven transgenes for human gene doping analysis

Abstract Gene doping is known as the manipulation of congenital traits by gene therapeutic approaches with the intent of illicit athletic performance enhancement. A panel prototype suitable for multiplex gene doping detection by combining multiplex Polymerase Chain Reaction (PCR)-amplification with Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) analysis was developed and examined for its specificity and sensitivity, and its applicability in human sports drug testing programs was assessed. The panel comprises 20 assays for exon-exon-junction detection of seven human transgenes (EPO, FST, GH1, IGF1, MSTN (propeptide), VEGFA, VEGFD), which have been considered as material to routine doping controls, in one reaction. Alongside, a suitable reference material (RM) was designed and tested for its utility. An estimated LOD95 of 1,500 cp / mL or 30 copies (cp) per reaction of the panel and 500 cp / mL or 10 cp per reaction of the RM was determined in plasmid-spiked human whole blood samples. The specificity and applicability of the panel and the RM was further determined by testing equine plasma samples obtained from an animal that received rAAV-delivered human transgenic EPO as well as 111 native human doping control samples.

Quantitative measurement of phenotype dynamics during cancer drug resistance evolution using genetic barcoding

Unveiling the structure, function and dynamics of StmPr1 in Stenotrophomonas maltophilia virulence

Abstract The increase in infections caused by multi-resistant Gram-negative bacteria, like Stenotrophomonas maltophilia, has become a growing health crisis worldwide. S. maltophilia poses a risk because of its tendency to opportunistically infecting patience for example through colonization of catheters in hospital environments using its intrinsic resistance against multiple antibiotics. Through the COVID-19 pandemic it gained more prominence by being a key pathogen in respiratory co-infections. This study will present a structural analysis of StmPr1, S. maltophilia’s main virulence factor, an excreted serine protease. Our study outline structure and functional aspects of StmPr1, revealing a unique autoproteolytic activity resulting in a shortened version of the active enzyme. We also investigated the potential of two groups of peptide-based inhibitors, one being acetyl- and the other being boron-based inhibitors. The focus here lies on Bortezomib, a boron-based serine protease inhibitor, and its potential therapeutic use against S. maltophilia. We provide a structure-function analysis which includes X-ray crystallography data with resolutions ranging from 1.64 to 2.08 Å, molecular dynamic simulations and small-angle X-ray scattering (SAXS) experiments. These data provide a deeper understanding of StmPr1’s resilience and mechanisms, while highlighting the relevance of StmPr1’s C-terminal extension for correct folding and its stability. Moreover, it also shows that StmPr1 is promising target for further drug discovery investigations to identify compounds and drugs to treat S. maltophilia infections.

Author Correction: ERK and USP5 govern PD-1 homeostasis via deubiquitination to modulate tumor immunotherapy

Aetiology and antibiotic susceptibility of bacterial keratitis at a referral centre in southern Sweden

Abstract This was a retrospective cross-sectional study evaluating the aetiology and antibiotic susceptibility in patients treated for suspected bacterial keratitis at Skåne University Hospital during 2019. Inclusion criteria: eyes with bacterial keratitis. Exclusion criteria: co-infection with other microbes. Primary outcome parameters: predisposing factors, causative pathogens and antibiotic susceptibility. Secondary outcome parameter: antibiotic treatment. A total of 255 cases met the inclusion criteria. Of these, 149 (58%) occurred in contact lens wearers. Corneal cultures, when performed, were positive in 51% of cases. For eyes which had received antibiotic treatment prior to corneal culture (n = 36), the proportion of positive cultures was 50%. Ulcers < 1 mm were less likely to yield a positive culture than those ≥ 1 mm. The most frequently isolated bacteria were coagulase-negative staphylococci (48%). Antibiotic resistance rates were lowest to levofloxacin (0%), ciprofloxacin (2%) and chloramphenicol (4%), and highest to fusidic acid (47%) and clindamycin (19%). The low proportion of positive cultures from small ulcers suggests that these warrant a different diagnostic approach. Furthermore, corneal cultures from eyes with ongoing antibiotic treatment were positive to the same extent as those from untreated eyes, suggesting that discontinuation of antibiotic treatment before re-culturing might not be necessary.

Bringing weak transitions to light

Abstract Weak transitions between quantum states are of fundamental importance for a broad range of phenomena from analytical biochemistry to precision physics, but generally challenge experimental detection. Due to their small cross sections scaling with the absolute square of their transition matrix elements, spectroscopic measurements often fail in particular in the presence of competing background processes. Here we introduce a general concept to break this scaling law and enhance the transition probability by exploiting a stronger laser-coupled pathway to the same excited state. We demonstrate the concept experimentally by attosecond transient absorption spectroscopy in helium atoms. The quasi-forbidden transitions from the ground state 1 s 2 to the weakly coupled doubly excited 2 p 3 d and s p 2,4− states are boosted by an order of magnitude. Enhancing single-photon-suppressed transitions can find widespread applicability, from spectral diagnostics of complex molecules in life and chemical sciences to precision spectroscopy of weak transitions in metastable atomic nuclei in the search for new physics.

Directional protection scheme using impedance approach for transmission lines

Abstract Identifying the direction of fault is an essential mission of the transmission line protective scheme. This paper discusses a direction protective technique based on a positive impedance approach. The samples of the instantaneous positive sequence voltage component and the instantaneous positive sequence current component are used to determine the impedance approach and complete the Z matrix values. The fault direction can be determine using Z matrix values. Different configurations of the power system are utilized to examine the proposed protective scheme. Software ATP-EMTP (Simulation experiments) verified the feasibility of the presented scheme. To verify the capability and accuracy of presented scheme, it is examined by many fault scenarios such as high fault resistance, far end fault, cross-country fault, power flow change, single pole tripping, CT saturation and noise impact. In addition, the validity of the presented scheme is compared with other protection directional schemes.

‘Super-healing’ animals inspire human treatments

Efficacy of baloxavir marboxil against bovine H5N1 virus in mice

Functional transposition of renal functions to the posterior intestine during maturation in male three-spined stickleback

Abstract During the breeding season, the male stickleback proximal tubule of the kidney undergoes hypertrophy. This is due to the synthesis of the nest building protein spiggin, in response to increased levels of 11-ketotestosterone. The increased protein synthesis that is initiated during breeding alters the kidney function and the ability to secrete excess water, to osmoregulate, in fresh water. It has earlier been shown that there exist organ specific differences in transport proteins between mature and non-mature three-spined stickleback. To understand the molecular mechanisms compensating for kidney functions, this study examined transport genes responsible for functional changes between the kidney and intestine. RNA sequencing was performed on castrated and 11-ketoandrostenedione (11KA)-treated male stickleback. Results showed organ-specific responses: 2,549 differentially expressed genes (DEGs) in the kidney and 885 in the posterior intestine, with 210 shared between the organs. Solute transporters, aquaporin 10a and cadherin-17, were upregulated in the posterior intestine but downregulated in the kidney in 11KA treated males. Enrichment analysis revealed distinct biological processes, primarily involving solute transporters, indicating functional adaptation. While amino acid and ion transport were downregulated in the kidney, compensatory transport was observed in the posterior intestine. However, cellular hexose transporters were downregulated in both organs, suggesting a reduction in glucose absorption and passive water diffusion. The present study shows that androgens alter the expression of cellular transporters and redirect functions of the kidney to the posterior intestine. The results also indicate reduced glucose absorption in breeding, male three-spined stickleback.

Developing astronomers in Africa: ‘We wanted to create a discipline’

In vitro generation of a ureteral organoid from pluripotent stem cells

Tuning surface properties of thiophene-based thin films on glass substrates for cancer cell adhesion, drug release control, and computational analysis

Abstract This study explores the potential of six novel thiophene derivative thin films (THIOs) for reducing cancer cell adhesion and enhancing controlled drug release on inert glass substrates. Thiophene derivatives 3a–c and 5a–c were synthesized and characterized using IR, 1H NMR, 13C NMR, and elemental analysis before being spin-coated onto glass to form thin films. SEM analysis and roughness measurements were used to assess their structural and functional properties. Biological evaluations demonstrated that the films significantly reduced HepG2 liver cancer cell adhesion (~ 78% decrease vs. control) and enabled controlled drug release, validated through the Korsmeyer-Peppas model (R2 > 0.99). Theoretical studies, including in-silico target prediction, molecular docking with JAK1 (PDB: 4E4L), and DFT calculations, provided insights into the electronic properties and chemical reactivity of these compounds. Notably, compound 5b exhibited the best binding energy (-7.59 kcal/mol) within the JAK1 pocket, aligning with its observed apoptotic behavior in cell culture. DFT calculations further revealed that 5b had the lowest calculated energy values; -4.89 eV (HOMO) and − 3.22 eV (LUMO), and the energy gap was found to be 1.66 eV, supporting its role in JAK1 inhibition and cancer cell adhesion reduction. These findings underscore the promise of thiophene derivatives in biomedical applications, potentially leading to safer surgical procedures and more effective localized drug delivery systems.

Halogen abundance evidence for the formation and metasomatism of the primary lunar crust

A psychometric study of the team psychological safety scale and sport psychological safety inventory in Swedish elite sports

Abstract Studies investigating psychological safety in sports and non-sports contexts have mostly utilized the universal Team Psychological Safety Scale (TPSS) aimed for performance development in professional teams. The Sport Psychological Safety Inventory (SPSI) has recently been introduced for psychological safety measurement specifically in sports. The aim of this study was to compare the psychometric properties of the TPSS and the SPSI within an elite sport context. A cross-sectional survey was used to collect data for assessment of the internal consistency, factorial validity, construct validity and measurement invariance of the TPSS and the SPSI. Complete data sets were provided by 371 elite Athletics athletes (track and field) and orienteers. Both the TPSS (ω = 0.72) and the SPSI subscales (range: ω = 0.81-0.88) showed acceptable internal consistency. Confirmatory factor analyses indicated a mediocre to good model fit for the TPSS and the SPSI three-factor correlated structure. The TPSS and the SPSI subscale ‘mentally healthy environment’ showed a moderate correlation. Measurement invariance tests suggested the TPSS to be fully invariant across genders, while the SPSI was found non-invariant. The study shows that the TPSS appears sound for assessing psychological safety in elite sports, while caution is needed when using the SPSI.

Author Correction: PTEN deficiency reprogrammes human neural stem cells towards a glioblastoma stem cell-like phenotype

Rosemary essenitial oil counters MnO2 nanoparticle-induced fertility deficits in rats via antioxidant mechanisms and upregulation of StAR signalling

Abstract Manganese, an essential nutrient for male reproductive health, exerts dose-dependent effects, with excessive exposure—particularly to manganese dioxide nanoparticles (MnO 2 -NPs) from environmental or industrial sources inducing gonadal damage via oxidative stress, hormonal disruption, and impaired steroidogenesis. This study evaluated rosemary essential oil (REO) against MnO 2 -NP-induced reproductive dysfunction in male rats. Seventy-two Sprague–Dawley rats (130 ± 10 g) were divided into six groups (n = 12): Group I (deionized water), Group II (saline), Group III (MnO 2 -NP, 100 mg/kg bw/day), Group IV (REO, 250 mg/kg/day), Protective Group V (REO pre-treatment + MnO 2 -NPs), and Therapeutic Group VI (MnO 2 -NPs + REO co-treatment) for 56 days. MnO 2 -NP exposure caused testicular injury, marked by elevated lipid peroxidation (↑malondialdehyde, ↑nitric oxide), suppressed antioxidants (↓total antioxidant capacity, ↓catalase, ↓glutathione), impaired sperm parameters (motility, count, morphology), and altered serum hormone levels (follicle-stimulating hormone, luteinizing hormone, testosterone). These effects correlated with downregulated steroidogenesis genes ( StAR , HSD-3β, CYP11A1). Both Protective and Therapeutic REO treatment mitigated MnO 2 -NPs oxidative stress, restored hormonal balance, and normalized gene expression. Histopathology revealed reduced seminiferous tubule degeneration and enhanced spermatogenesis in REO groups. Findings demonstrate REO’s efficacy in alleviating MnO 2 -NPsinduced reproductive toxicity via antioxidant and steroidogenic modulation, positioning REO as a promising therapeutic against nanomaterial-induced gonadotoxicity.

Effects of taurine, brimonidine and betaxolol on oscillation modulation and stimulation efficiency in degenerated rd10 mouse retinas

Abstract The rd10 mouse is a widely used model for degenerative retinal diseases such as retinitis pigmentosa (RP). Its retina shows rhythmic spontaneous activity at a frequency of three to seven Hz, and the retinal ganglion cells (RGCs) are less electrically excitable. We hypothesize that the electrical excitability can be improved by suppressing the oscillations using the neuroprotective drugs 2-aminoethanesulphonic acid (taurine), brimonidine and betaxolol. These are involved in calcium homeostasis and may play a crucial role in neuroprotection and excitotoxicity by preventing Ca2+ overload. Spontaneous activity and responses to electrical stimulation of isolated retinas from 3- to 4-month-old rd10 mice were recorded using multielectrode arrays. At defined times, the neuroprotectants were repeatedly added to the medium according to a standardized protocol to analyze the reproducibility and reversibility of their effects. Taurine and betaxolol significantly reduced oscillations and bursting behavior and ameliorated electrical efficiency. Brimonidine only reduced the frequency of oscillations. The effects on oscillation, spontaneous firing frequency, bursting behavior and stimulation efficiency were reproducible and reversible. The drugs tested appear to be promising therapeutic candidates for improving the residual function of RGCs. They will be further investigated and combined with other RP treatments, such as retinal prostheses, in the future.

Special endurance coefficients enable the evaluation of running performance

Abstract Running performance from sprint to long distance is largely determined by the interplay between basic speed and endurance. Existing power-law, physiological, and theoretical models describe and explain the characteristic decline in pace with increasing distance. However, normative and statistically validated measures that capture both the average and variability of pace decline across standard track distances remain incomplete. To address this gap, we analysed over 14,000 race times from competitive male runners and introduce the coefficient of special endurance (KsA), a novel metric that quantifies relative pace loss between adjacent race distances, from 100/200 to 5000/10,000 m. The KsA values obtained for seven distance pairs are nearly constant over decades in national runners, show low variability, and predict race times with less than one percent. The KsA-based reference ranges allow performance to be evaluated from the international to the regional level. This provides specific insight into runners’ strengths, weaknesses and progression for individualizing training, selecting the most promising race distance, and identifying and developing talent. Overall, we provide empirically derived KsA values that serve as statistical norms for pace loss from 100 m to 10,000 m to evaluate running performance of males. The current approach should also be applicable to women, juniors, and road runners.